Experience with <sup>177</sup>Lu-Dotatate in patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET): Report from a single urban cancer center.
Authors: Aria Kieft, Yahya Ibrahim, Gregory Dyson, Geoffrey Baran, Asfar S. Azmi, Mohammed Najeeb Al Hallak, Anthony Frank Shields, Nitin Vaishampayan, Philip Agop Philip
Journal: Journal of Clinical Oncology (2022)

e18688 Background: 177 Lu-Dotatate is FDA approved for advanced well differentiated (WD) midgut neuroendocrine tumors (NETs). However, questions remain about tolerability and efficacy in patients (pts) with higher grade disease, more than one prior line of treatment, and in non-ileal primaries. Methods: This is a retrospective analysis of pts with histologically proven WD metastatic GEP-NETs who received 177 Lu-Dotatate at a single racially diverse urban cancer center. Patients had disease that progressed on systemic therapy that included somatostatin analog (SSA), and radiotracer uptake at disease sites using 68 Gallium-Dotate PET/CT. ECOG performance score (PS) was 0 to 2. 177 Lu-Dotatate was administered in 200 mCi doses every 8 weeks for a total of 4 cycles and a maximum of 800 mCi. Patients were followed with serial CT scan and/or abdominal MRI with best objective response per RECIST criteria. Results: Fifty-one pts were treated between December 2017 and August 2021. Thirty-eight pts completed a minimum 3-month follow-up imaging. Median age was 64 years, 59% were female, 66% identified as white, 26% as Black, 8% as other. Most frequent primary sites were small intestine (64%) and. All had metastatic disease involving the liver except for one pt. Median time from diagnosis to 177 Lu-Dotatate was 51 months (3-201). CTCAE grade 3/4 hematologic toxicity was seen in 6 of 51 pts (12%). Grade 3/4 thrombocytopenia occurred in 3 pts, grade 3/4 leukopenia occurred in 2 pts and grade 3 anemia occurred in 1 pt. A single pt developed myelodysplastic syndrome 1 year after 177 Lu-Dotatate. Non-white pts had significantly higher risk of grade 1 elevated creatinine at 38% vs 6% in those who identified as white (p = 0.015). Of the 37 pts who reached 3-month follow-up, 27% had partial response, 43% had a mixed/stable response, and 30% had progressive disease. Only gender demonstrated significant difference; with male gender associated with worse response categories (p = 0.001). Median OS was 3.09 years. Metastatic disease in the liver only was associated with significantly worse OS (p = 0.015) compared to liver and other tissues. The median PFS was 1.36 years. Metastatic disease in the liver only was associated with significantly worse PFS (p = 0.043). Higher tumor grade neared significant association with worse PFS (p = 0.053). There was no difference in PFS by race, primary tumor site (pancreatic vs small bowel), PS, prior treatment history or time to first 177 Lu-Dotatate. Conclusions: Diverse patients with WD GEP-NETs treated at this single urban cancer center with 177 Lu-Dotatate demonstrated acceptable toxicity. Median PFS and OS were inferior to reported outcomes in NETTER-1 probably because of differences in treatment timing and patient populations. Possible variables associated with difference in outcome include pattern of metastatic disease and tumor grade.